DISUBSTITUTED 5(3)-PYRAZOLE CARBOXYLATES AND A PROCESS FOR THEIR PREPARATION FROM ENOLATES AND FLUOROALKYLAMINOREAGENTS (FAR) REAGENTS

Abstract

The present invention relates to disubstituted 5(3)-pyrazole carboxylates of the formula (Ia) or (Ib) and a process for their preparation

##STR00001## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4 and n are defined as above.

Claims

1. Process for preparation of disubstituted 5(3)-pyrazole carboxylate of formula (Ia) or (Ib), ##STR00019## wherein R.sup.1 is selected from H, (C.sub.1-C.sub.6)alkyl, phenyl or 2-pyridyl, R.sup.2 is selected from H, (C.sub.1-C.sub.12)alkyl or (C.sub.3-C.sub.8)cycloalkyl, R.sup.3 is selected from (C.sub.1-C.sub.12)alkyl, (C.sub.1-C.sub.3)haloalkyl, (C.sub.3-C.sub.8)cycloalkyl, (C.sub.6-C.sub.12)aryl, (C.sub.1-C.sub.3)alkyl(C.sub.6-C.sub.12)aryl and (C.sub.6-C.sub.12)aryl(C.sub.1-C.sub.6)alkyl, R.sup.4 is selected from (C.sub.1-C.sub.6)haloalkyl and (C.sub.1-C.sub.3)haloalkoxy(C.sub.1-C.sub.6)haloalkyl and n is 0, 1 or 2, comprising (A), wherein an α,α-difluoroalkylamino reagent (FAR) of formula (III), ##STR00020## wherein R.sup.4 is defined as above and R.sup.6 and R.sup.7 are each independently selected from (C.sub.1-C.sub.6)alkyl, (C.sub.3-C.sub.8)cycloalkyl, (C.sub.6-C.sub.12)aryl or together with the nitrogen atom to which they are bonded may form a five- or six-membered ring, is first converted into one or more compounds of formula (VI) in the presence of a Lewis Acid [L] ##STR00021## where R.sup.4, R.sup.6 and R.sup.7 are defined as for formula (III) and [LF].sup.− is an anion formed from the Lewis Acid [L] and one fluorine atom from compound (III), and then the compound of formula (VI) is reacted with one or more enolates of formula (II), ##STR00022## wherein R.sup.5 is selected from (C.sub.1-C.sub.12)alkyl or (C.sub.3-C.sub.8)cycloalkyl, R.sup.3 and n are defined as above, m is 1 or 2 and Cat.sup.m+ is selected from alkaline metal cations (with m=1), alkaline earth metal cations (with m=2), organic ammonium cations (with m=1) or organic phosphonium cations (with m=1), to form the compound of formula (IV), ##STR00023## wherein n, [LF].sup.−, R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 are defined as above, and further comprising (B), wherein cyclization with a hydrazine of formula (V)
NH.sub.2—NH—R.sup.1  (V), wherein R.sup.1 is defined as above, takes place to form the compound of formula (Ia) or (Ib).

2. Process according to claim 1, wherein the radicals in formula (Ia), (Ib), (II), (III), (IV), (V) and (VI) are defined as R.sup.1 is selected from H, (C.sub.1-C.sub.6)alkyl, phenyl or 2-pyridyl, R.sup.2 is selected from H, (C.sub.1-C.sub.6)alkyl or (C.sub.3-C.sub.6)cycloalkyl, R.sup.3 is selected from (C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.3)haloalkyl, (C.sub.3-C.sub.6)cycloalkyl, (C.sub.6-C.sub.9)aryl, (C.sub.1-C.sub.3)alkyl(C.sub.6-C.sub.9)aryl and (C.sub.6-C.sub.9)aryl(C.sub.1-C.sub.3)alkyl, R.sup.4 is selected from (C.sub.1-C.sub.6)haloalkyl and (C.sub.1-C.sub.3)haloalkoxy(C.sub.1-C.sub.6)haloalkyl, R.sup.5 is selected from (C.sub.1-C.sub.6)alkyl or (C.sub.3-C.sub.6)cycloalkyl, n is 0, 1 or 2, R.sup.6 and R.sup.7 are each independently selected from (C.sub.1-C.sub.6)alkyl, (C.sub.3-C.sub.6)cycloalkyl, (C.sub.6-C.sub.12)aryl or R.sup.6 and R.sup.7 together with the nitrogen atom to which they are bonded may form a five- or six-membered ring, m is 1 and Cat.sup.m+ is selected from alkaline metal cations, optionally from Li.sup.+, Na.sup.+, K.sup.+ and Cs.sup.+, organic ammonium cations, optionally (R.sup.8).sub.4N.sup.+ or organic phosphonium cations, optionally (phenyl).sub.4P.sup.+, wherein R.sup.8 are each independently selected from (C.sub.1-C.sub.6)alkyl.

3. Process according to claim 1, wherein the radicals in formula (Ia), (Ib), (II), (III), (IV), (V) and (VI) are defined as R.sup.1 is selected from H, (C.sub.1-C.sub.6)alkyl or phenyl, R.sup.2 is selected from H or (C.sub.1-C.sub.6)alkyl, R.sup.3 is selected from (C.sub.1-C.sub.6)alkyl, R.sup.4 is selected from (C.sub.1-C.sub.6)haloalkyl and (C.sub.1-C.sub.3)haloalkoxy(C.sub.1-C.sub.6)haloalkyl, wherein the halogen is selected from fluoro and/or chloro, R.sup.5 is selected from (C.sub.1-C.sub.6)alkyl, n is 0, 1 or 2, R.sup.6 and R.sup.7 are each independently selected from (C.sub.1-C.sub.6)alkyl, m is 1 and Cat.sup.m+ is selected from Li.sup.+, Na.sup.+, K.sup.+, Cs.sup.+ or Me.sub.4N.sup.+.

4. Process according to claim 1, wherein the radicals in formula (Ia), (Ib), (II), (III), (IV), (V) and (VI) are defined as R.sup.1 is selected from H, methyl, ethyl or phenyl R.sup.2 is selected from H, methyl or ethyl, R.sup.3 is selected from methyl or ethyl R.sup.4 is selected from difluoromethyl (CF.sub.2H), chlorofluoromethyl (CHFCl), 1,2,2,2-tetrafluoroethyl (CF.sub.3CFH), pentafluoroethyl (C.sub.2F.sub.5) and trifluoromethoxyfluoromethyl (CF.sub.3OCFH), R.sup.5 is selected from (C.sub.1-C.sub.3)alkyl, n is 2, R.sup.6 and R.sup.7 are methyl, m is 1 and Cat+ is selected from Li.sup.+, Na.sup.+ or K.sup.+.

5. Process according to claim 1, wherein the radicals in formula (Ia), (Ib), (II), (III), (IV), (V) and (VI) are defined as R.sup.1 is selected from H, methyl or phenyl, R.sup.2 is selected from H, methyl or ethyl, R.sup.3 is methyl, R.sup.4 is selected from difluoromethyl (CF.sub.2H), chlorofluoromethyl (CHFCl), 1,2,2,2-tetrafluoroethyl (CF.sub.3CFH), pentafluoroethyl (C.sub.2F.sub.5) and trifluoromethoxyfluoromethyl (CF.sub.3OCFH), R.sup.5 is selected from methyl or ethyl, n is 2, R.sup.6 and R.sup.7 are methyl, m is 1 and Cat.sup.m+ is Na.sup.+ or K.sup.+.

6. The process according to claim 1, wherein the compound of formula (III) is selected from 1,1,2,2-tetrafluoroethyl-N, N-dimethylamine (TFEDMA), 1,1,2,2-tetrafluoroethyl-N, N-diethylamine, 1,1,2-trifluoro-2-(trifluoromethyl)ethyl-N, N-dimethylamine, 1,1,2-trifluoro-2-(trifluoromethyl)ethyl-N, N-diethylamine (Ishikawa's reagent), 1,1,2-trifluoro-2-chloroethyl-N,N-dimethylamine and 1,1,2-trifluoro-2-chloroethyl-N,N-diethylamine (Yarovenko's reagent) or 1,1,2-trifluoro-N, N-dimethyl-2-(trifluoromethoxy)ethanamine.

7. The process according to claim 1, wherein the Lewis Acid is selected from BF.sub.3, AlCl.sub.3, SbCl.sub.5, SbF.sub.5, PF.sub.5 or ZnCl.sub.2.

8. The process according to claim 1, wherein [LF].sup.− stands for BF.sub.4, AlCl.sub.3F.sup.−, SbCl.sub.5F.sup.−, SbF.sub.6.sup.−, PF.sub.6.sup.− or ZnCl.sub.2F.sup.−.

9. The process according to claim 1, wherein (A) is effected at one or more temperatures of −20° C. to +60° C.

10. The process according to claim 1, wherein reaction of compound (II) with the activated FAR (VI) is optionally effected in presence of a base.

11. The process according to claim 10, wherein the base is selected from tri(C.sub.1-C.sub.4)alkylamines, pyridines, (C.sub.1-C.sub.4)alkylpyridines, 8-diazabicyclo[5.4.0]undecene (DBU), alkali metal hydroxides, alkali metal carbonates, alkali metal (C.sub.1-C.sub.4)alkoxides or alkali metal fluorides.

12. The process according to claim 1, wherein (B) is effected at one or more temperatures of −20° C. to +80° C.

13. The process according to claim 1, wherein the process is carried out in the presence of a suitable solvent and (B) is effected without changing solvent after (A).

14. Intermediate of formula (IV) ##STR00024## Wherein R.sup.1 is selected from H, (C.sub.1-C.sub.6)alkyl, phenyl or 2-pyridyl, R.sup.2 is selected from H, (C.sub.1-C.sub.12)alkyl or (C.sub.3-C.sub.8)cycloalkyl, R.sup.3 is selected from (C.sub.1-C.sub.12)alkyl, (C.sub.1-C.sub.3)haloalkyl, (C.sub.3-C.sub.8)cycloalkyl, (C.sub.6-C.sub.12)aryl, (C.sub.1-C.sub.3)alkyl(C.sub.6-C.sub.12)aryl and (C.sub.6-C.sub.12)aryl(C.sub.1-C.sub.6)alkyl, R.sup.4 is selected from (C.sub.1-C.sub.6)haloalkyl and (C.sub.1-C.sub.3)haloalkoxy(C.sub.1-C.sub.6)haloalkyl and n is 0, 1 or 2, R.sup.6 and R.sup.7 are each independently selected from (C.sub.1-C.sub.6)alkyl, (C.sub.3-C.sub.8)cycloalkyl, (C.sub.6-C.sub.12)aryl or together with the nitrogen atom to which they are bonded may form a five- or six-membered ring, and [LF].sup.− is an anion formed from a Lewis Acid [L] and one fluorine atom.

15. Intermediate according to claim 14, wherein [LF].sup.− stands for BF.sub.4.sup.−.

16. Disubstituted 5(3)-pyrazole carboxylate of formula (Ia) or (Ib), ##STR00025## wherein R.sup.1 is selected from H, (C.sub.1-C.sub.6)alkyl, phenyl or 2-pyridyl, R.sup.2 is selected from (C.sub.1-C.sub.12)alkyl or (C.sub.3-C.sub.8)cycloalkyl, R.sup.3 is selected from (C.sub.1-C.sub.12)alkyl, (C.sub.1-C.sub.3)haloalkyl, (C.sub.3-C.sub.8)cycloalkyl, (C.sub.6-C.sub.12)aryl, (C.sub.1-C.sub.3)alkyl(C.sub.6-C.sub.12)aryl and (C.sub.6-C.sub.12)aryl(C.sub.1-C.sub.6)alkyl, R.sup.4 is selected from (C.sub.1-C.sub.6)haloalkyl and (C.sub.1-C.sub.3)haloalkoxy(C.sub.1-C.sub.6)haloalkyl and n is 0, 1 or 2.

17. Disubstituted 5(3)-pyrazole carboxylate of formula (Ia) or (Ib) according to claim 16, wherein R.sup.1 is selected from H, (C.sub.1-C.sub.6)alkyl, phenyl or 2-pyridyl, R.sup.2 is selected from (C.sub.1-C.sub.6)alkyl or (C.sub.3-C.sub.6)cycloalkyl, R.sup.3 is selected from (C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.3)haloalkyl, (C.sub.3-C.sub.6)cycloalkyl, (C.sub.6-C.sub.9)aryl, (C.sub.1-C.sub.3)alkyl(C.sub.6-C.sub.9)aryl and (C.sub.6-C.sub.9)aryl(C.sub.1-C.sub.3)alkyl, R.sup.4 is selected from (C.sub.1-C.sub.6)haloalkyl and (C.sub.1-C.sub.3)haloalkoxy(C.sub.1-C.sub.6)haloalkyl and n is 0, 1 or 2.

18. Disubstituted 5(3)-pyrazole carboxylate of formula (Ia) or (Ib) according to claim 16, wherein R.sup.1 is selected from H, (C.sub.1-C.sub.6)alkyl or phenyl, R.sup.2 is selected from (C.sub.1-C.sub.6)alkyl, R.sup.3 is selected from (C.sub.1-C.sub.6)alkyl, R.sup.4 is selected from (C.sub.1-C.sub.6)haloalkyl and (C.sub.1-C.sub.3)haloalkoxy(C.sub.1-C.sub.6)haloalkyl, wherein the halogen is selected from fluoro and/or chloro and n is 0, 1 or 2.

19. Disubstituted 5(3)-pyrazole carboxylate of formula (Ia) or (Ib) according to claim 16, wherein R.sup.1 is selected from H, methyl, ethyl or phenyl R.sup.2 is selected from methyl or ethyl, R.sup.3 is selected from methyl or ethyl, R.sup.4 is selected from difluoromethyl (CF.sub.2H), chlorofluoromethyl (CHFCl), 1,2,2,2-tetrafluoroethyl (CF.sub.3CFH), pentafluoroethyl (C.sub.2F.sub.5) and trifluoromethoxyfluoromethyl (CF.sub.3OCFH) and n is 2.

20. Disubstituted 5(3)-pyrazole carboxylate of formula (Ia) or (Ib) according to claim 16, wherein R.sup.1 is selected from H, methyl or phenyl, R.sup.2 is selected from methyl or ethyl, R.sup.3 is methyl, R.sup.4 is selected from difluoromethyl (CF.sub.2H), chlorofluoromethyl (CHFCl), 1,2,2,2-tetrafluoroethyl (CF.sub.3CFH), pentafluoroethyl (C.sub.2F.sub.5) and trifluoromethoxyfluoromethyl (CF.sub.3OCFH) and n is 2.

Description

EXAMPLES

[0152] The invention is illustrated by but not limited to the following examples:

Example 1

[(Z/E)-1-(difluoromethyl)-4-ethoxy-3-hydroxy-2-methyl-4-oxo-but-2-enylidene]-dimethyl-ammoniumtetrafluoroborate

[0153] ##STR00012##

[0154] BF.sub.3.OEt.sub.2 (0.12 ml, 1.0 mmol) was added to a solution of 1,1,2,2-tetrafluoroethyl-N,N-dimethylamine (TFEDMA) (0.12 ml, 1.0 mmol) in dry dichloromethane (1 ml) under argon in a Teflon flask. The solution was stirred at room temperature for 15 min, before the dichloromethane was removed under reduced pressure. The solid residue was then taken up in acetonitrile (1 ml) and (0,216 g, 1.0 mmol) of sodium 3-ethoxy-1-(methylsulfonyl)-3-oxoprop-1-en-2-olate and (0,316 g, 4 mmol) pyridine was added in CD.sub.3CN (2 ml) and the mixture was stirred at room temperature for 10 h. The solvent was evaporated in vacuum and the residue then analysed by .sup.1H, .sup.13C and .sup.19F NMR.

[0155] .sup.1H NMR (600 MHz, CD.sub.3CN-d.sub.3) δ ppm 1.29 (br t, J=7.13 Hz, 4H) 3.22 (s, 3H) 3.44 (br s, 6H) 4.24 (q, J=7.23 Hz, 3H) 6.90-7.09 (m, 1H) 8.99-9.34 (m, 1H)

[0156] .sup.13C NMR (151 MHz, CD.sub.3CN-d.sub.3) δ ppm 14.20 (s, 1C) 46.42 (s, 1C) 46.65-47.52 (m, 1C) 62.96 (s, 1C) 104.90-105.03 (m, 1C) 111.25 (t, J=248.91 Hz, 1C) 165.03-165.52 (m, 1C) 166.44 (s, 1C) 177.33 (s, 1C).

[0157] .sup.19F NMR (CDCl.sub.3, 282 MHz): δ ppm −117.3 (CHF.sub.2, J.sub.F-H=53.6 Hz), −150 (BF.sub.4)

Example 2

Ethyl 5-(difluoromethyl)-2-methyl-4-methylsulfonyl-pyrazole-3-carboxylate

[0158] ##STR00013##

[0159] BF.sub.3CH.sub.3CN complex (17 wt. % solution) (2.17 g, 20 mmol) was added to a solution of TFEDMA (2.86 g, 20 mmol) in 25 ml CH.sub.3CN under argon in a Teflon flask. The solution was stirred at room temperature for 15 min, before (3.2 g, 15 mmol) of sodium 3-ethoxy-1-(methylsulfonyl)-3-oxoprop-1-en-2-olate and (4.7 g, 60 mmol) pyridine were added at 10° C. and the mixture was stirred at room temperature for 10 h. The mixture was cooled to −10° C. and (1.38 g 30 mmol) of methylhydrazine was added to the reaction mixture. The formed suspension was stirred for 4 h at RT and 100 ml of water were added. The product was extracted with ethylacetate, the organic solution washed with 10 ml (10 wt. %) HCl and water and the organic solvent was evaporated to furnish a pale yellow solid, which was recrystallized from methycyclohexane.

[0160] Yield 3.18 g, 75% of theory.

[0161] .sup.1H NMR (DMSO-d.sub.6, 600 MHz): δ ppm 7.25 (t, J=53.3 Hz, 1H) 4.43 (q, J=7.2 Hz, 2H) 4.09 (s, 3H) 1.36 (t, J=7.1 Hz, 3H)

[0162] .sup.13C NMR (151 MHz, DMSO-d.sub.6) δ ppm 13.63 (s, 1C) 40.46 (s, 1C) 44.92 (s, 1C) 63.25 (s, 1C) 108.90 (t, J=236.56 Hz, 1C) 122.47 (s, 1C) 135.77 (s, 1C) 143.14 (t, J=24.85 Hz, 1C) 157.63 (s, 1C)

[0163] .sup.19F NMR (CFCl.sub.3, 282 MHz): δ ppm −115.06, (d)

Example 3

5-(difluoromethyl)-2-methyl-4-methylsulfonyl-pyrazole-3-carboxylic acid

[0164] ##STR00014##

[0165] Ethyl 5-(difluoromethyl)-2-methyl-4-methylsulfonyl-pyrazole-3-carboxylate (2.83 g, 10 mmol) in toluene (15 ml) was mixed with an 8N aqueous sodium hydroxide solution (100 ml) and stirred at 50° C. for 3 h. The phases were separated and the water phase was acidified to pH 1 with 6N HCl. The formed precipitate was filtered off and dried.

[0166] Yield 2.3 g, 90%, colourless solid, m.p. 168° C.

[0167] .sup.1H NMR (DMSO-d.sub.6, 600 MHz): δ ppm 7.24 (t, J=53.3 Hz, 1H) 4.08 (s, 3H) 3.39 (s, 3H)

[0168] .sup.13C NMR (151 MHz, DMSO-d.sub.6): δ ppm: 40.4 (s, 1C) 44.92 (s, 1C) 109.0 (t, J=236.56 Hz, 1C) 121.9 (s, 1C) 137.5 (s, 1C) 143.0 (t, J=24.85 Hz, 1C) 159.3 (s, 1C)

[0169] .sup.19F NMR (CFCl.sub.3, 282 MHz): δ ppm −114.61, (d)

Example 4

Ethyl 5-(difluoromethyl)-1-methyl-4-methylsulfonyl-pyrazole-3-carboxylate

[0170] ##STR00015##

[0171] BF.sub.3CH.sub.3CN complex (17 wt. % solution) (2.17 g, 20 mmol) was added to a solution of TFEDMA (2.86 g, 20 mmol) in 25 ml CH.sub.3CN under argon in a Teflon flask. The solution was stirred at room temperature for 15 min, before the (3.2 g, 15 mmol) of sodium 3-ethoxy-1-(methylsulfonyl)-3-oxoprop-1-en-2-olate and (4.7 g, 60 mmol) of pyridine were added at 10° C. and the mixture was stirred at room temperature for 10 h. The solvent and volatile products were removed in vacuum (20 mbar) and the residue was taken up in 30 ml ethanol. The solution was cooled to 10° C. and (1.38 g, 30 mmol) of methylhydrazine was added to the reaction mixture within 30 min. The formed suspension was stirred for 4 h at RT and 100 ml of water were added. The product was extracted with ethylacetate, the organic solution was washed with 10 ml (10 wt. %) HCl and water and the organic solvent was evaporated to furnish a pale yellow solid, which was recrystallized from methycyclohexane.

[0172] Yield 3.3 g., 78% of theory.

[0173] .sup.1H NMR (600 MHz, DMSO-d.sub.6) δ ppm 1.32 (s, 3H) 3.50 (s, 3H) 4.11 (s, 3H) 4.34-4.38 (m, 2H) 7.42-7.61 (m, 1H).

[0174] .sup.13C NMR (151 MHz, DMSO-d.sub.6) δ ppm 13.99 (s, 1C) 40.49 (s, 1C) 44.60 (s, 1C) 62.12 (s, 1C) 123.87 (s, 1C) 136.88 (s, 1C) 140.54-141.18 (m, 1C) 159.97 (s, 1C)

Example 5

Ethyl 5-(difluoromethyl)-1-methyl-4-methylsulfonyl-pyrazole-3-carboxylic acid

[0175] ##STR00016##

[0176] Ethyl 5-(difluoromethyl)-1-methyl-4-methylsulfonyl-pyrazole-3-carboxylate (2.83 g, 10 mmol) in toluene (15 ml) was mixed with an 8N aqueous sodium hydroxide solution (30 ml) and stirred at 50° C. for 3 h. The phases were separated and the water phase was acidified to pH 1 with 6N HCl. The formed precipitate was filtered off and dried.

[0177] Yield 2, 4 g, 95%, colourless solid, m.p. 186° C.

[0178] .sup.1H NMR (600 MHz, DMSO-d.sub.6) δ ppm 3.50 (s, 3H) 4.09 (s, 3H) 7.40-7.66 (m, 1H) 13.17-14.78 (m, 1H)

[0179] .sup.13C NMR (151 MHz, DMSO-d.sub.6) δ ppm 40.46 (t, J=3.46 Hz, 1C) 44.50 (s, 1C) 107.21 (t, J=236.26 Hz, 1C) 123.66 (s, 1C) 136.68 (t, J=25.15 Hz, 1C) 142.02 (s, 1C) 161.55 (s, 1C)

[0180] .sup.19F NMR (CFCl.sub.3, 282 MHz) δ ppm −115, 44, (d)

Example 6

Ethyl 5-(difluoromethyl)-4-methylsulfonyl-2-phenyl-pyrazole-3-carboxylate

[0181] ##STR00017##

[0182] BF.sub.3CH.sub.3CN complex (17 wt. % solution) (3.26 g, 30 mmol) was added to a solution of TFEDMA (4.3 g, 30 mmol) in 25 ml CH.sub.3CN under argon in a Teflon flask. The solution was stirred at room temperature for 15 min, before (3.2 g, 15 mmol) of sodium 3-ethoxy-1-(methylsulfonyl)-3-oxoprop-1-en-2-olate and (4.7 g, 60 mmol) pyridine were added at 10° C. and the mixture was stirred at room temperature for 10 h. The mixture was cooled to −10° C. and (3.2 g, 30 mmol) of Phenylhydrazine was added to the reaction mixture. The formed suspension was stirred for 4 h at room temperature and 100 ml of water were added. The product was extracted with ethylacetate, the organic solution washed with 10 ml (10 wt. %) HCl and water and the organic solvent was evaporated to furnish a pale yellow solid, which was recrystallized from ethanol/water.

[0183] Yield 4.17 g., 81% of theory.

[0184] 1H NMR (600 MHz, DMSO-d.sub.6) δ ppm 1.11 (t, J=7.13 Hz, 3H) 3.45 (s, 3H) 4.28 (q, J=7.16 Hz, 2H) 7.33-7.35 (m, 1H) 7.55-7.58 (m, 2H) 7.59-7.62 (m, 2H) 7.60-7.63 (m, 1H)

[0185] .sup.13C NMR (151 MHz, DMSO-d.sub.6) δ ppm 13.66 (s, 1C) 40.49 (s, 1C) 44.95 (s, 1C) 63.28 (s, 1C) 108.92 (s, 1C) 122.48 (t, J=3.61 Hz, 1C) 135.79 (s, 1C) 142.97-143.38 (m, 1C) 157.65 (s, 1C)

Example 7

5-(Difluoromethyl)-4-methylsulfonyl-2-phenyl-pyrazole-3-carboxylic acid

[0186] ##STR00018##

[0187] Ethyl 5-(difluoromethyl)-4-methylsulfonyl-2-phenyl-pyrazole-3-carboxylate (3.44 g, 10 mmol) in toluene (15 ml) was mixed with an 8N aqueous sodium hydroxide solution (142 ml) and stirred at 40° C. for 3 h. The phases were separated and water phase acidified to pH 1 with 6N HCl. The precipitate was filtered off and dried.

[0188] Yield 3 g, 95% of colourless solid, m.p. 187° C.

[0189] .sup.1H NMR (600 MHz, DMSO-d.sub.6) δ ppm 3.50 (s, 3H) 4.09 (s, 3H) 7.40-7.66 (m, 1H) 13.17-14.78 (m, 1H).

[0190] .sup.13C NMR (151 MHz, DMSO-d.sub.6) δ ppm 40.46 (t, J=3.46 Hz, 1C) 44.50 (s, 1C) 107.21 (t, J=236.26 Hz, 1C) 123.66 (s, 1C) 136.68 (t, J=25.15 Hz, 1C) 142.02 (s, 1C) 161.55 (s, 1C)